Diabetes, Parkinson's, Alzheimer's, Huntington's, heart disease, muscular dystrophy and osteoarthritis are some of degenerative diseases that would benefit from cell transplantation. However, the benefits of cell transplantation will not be fully realized unless customized, patient- specific cells become available. Current cell-based therapies that are being developed from human embryonic stem cells and adult stem cells would require life-long immuno-suppression in the majority of patients. Cells and tissues customized to the needs of a specific patient are not available and there are no published reports on the derivation of therapeutically useful cells from patient's own differentiated tissue. Only vertebrate eggs contain the biochemical machinery that has the ability to erase adult cell nuclear memory and replace it with the lost embryonic nuclear memory (de-differentiation), as demonstrated by animal cloning successes in several animal species. The objectives of the proposal are to de-differentiate human adult skin fibroblasts into stem-like cells using Xenopus egg extract, identify and characterize Xenopus egg extract components that are required for de-differentiation and validate the therapeutic utility of stem- like cells by inducing tumor formation in SCID mice. The project will develop stem-like de-differentiated cells from adult human fibroblasts with Xenopus egg extract; we will identify and characterized extract components required for de-differentiation and test stem-like cells for their developmental potential. De-differentiated cells can then be used to develop novel therapeutic, patient-specific (autologous) cells for cell therapy of degenerative diseases. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]